The overall aim of this project is to gain a better understanding of the impaired distributed neuronal network that underlies working memory deficits in schizophrenic patients. A key process that has been implicated in impaired executive function is working memory, the type of memory that is active and relevant for only short periods of time. Studies in animals and humans suggest that prefrontal cortical-medial temporal circuits are essential for working memory. This project will test the hypothesis that impairment in working memory in schizophrenia is associated with lower prefrontal cortical and medial temporal activity compared to matched healthy control subjects as measured by functional magnetic resonance imaging (FMRI) during performance of working memory tasks. The study uses a parametric design in which 3 different levels of memory delay (0.5, 1.5, and 3.5 s) and 3 different levels of task difficulty (3, 5, and 7 digits per stimulus) are presented. Prior to the FMRI session, the subjects are trained in in an MRI Simulator. The working memory conditions are the Delayed Memory Task (DMT) and Medium-delay Memory Task (MMT), designed to measure ability to retain a stimulus in working memory for 3.5 s. or 1.5 s respectively. The control task is an 'Immediate' Memory Task (IMT), similar to the DMT except that the delay period is only 0.5 s. The IMT controls for the sensorimotor and attentional elements of the DMT. All tasks have the same rate of motor behavior and the same number of salient (and non-salient) stimuli. Schizophrenic patients, who have been medication-free due to self-discontinuation of medication for at least 2 weeks immediately prior to scanning, and matched healthy control subjects undergo baseline FMRI sessions during performance of the working memory tasks. FMRI data are acquired with a 1.5 T GE Horizon LX MRI scanner using an echoplanar, gradient echo pulse sequence. Post-processing includes head motion correction, temporal autocorrelation correction, and normalization to the Talairach atlas. Statistical Parametric Mapping (SPM99) with small volume correction is used to test for significant changes in the specific regions of interest hypothesized in this study, and employs a Random Effects statistical model to account for between-subject variance. The performance of the subjects on the working memory tasks during the FMRI scans is utilized as a covariate in the analysis in order to control for individual differences in task performance.